Inducible CreERT2 mouse lines for characterization of retinal bipolar cell subtypes

Bipolar cells relay visual signals from photoreceptor cells to ganglion cells in the retina. Fifteen bipolar cell subtypes have been identified in the mouse retina. These subtypes are classified as ON and OFF bipolar cells based on their response to light stimulus or rod and cone bipolar cells based on their connection to photoreceptor cells. However, the unique structural and functional role of these subtypes in the processing of visual information is not fully known due to the inadequate tools and models available for their characterization. In this study, to trace the lineage and characterize Vsx1, Lhx3, and Lhx4 - expressing bipolar cell subtypes in developing and adult mouse retina, we developed inducible Cre lines under the promoter of Vsx1, Lhx3, and Lhx4 and crossed them with ChR2EYFP reporter mice. Lineages of cells expressing Vsx1, Lhx3, and Lhx4 after Cre induction in the adult and postnatal mouse retina were then characterized. ChR2EYFP expression driven by Vsx1-CreERT2 was detected in type 2, 6, and 7 bipolar cells, Lhx3-CreERT2 in type 1b, 2, and 6 bipolar cells, and Lhx4-CreERT2 in type 2, 3, 4, and 5 bipolar cells as well as cone photoreceptor cells in the adult mouse retina. These bipolar cell subtype-specific inducible Cre mouse lines serve as efficient tools for elucidation of the mechanisms that control bipolar cell subtype development and function in the retina. Significance StatementBipolar cells are central connectors of the outer and inner retina and initiate processing of complex visual information. Bipolar cells differentiate into more than fifteen subtypes during development, and their structural diversity has been well studied. However, the unique contribution of these subtypes to the processing of visual information is poorly understood due to inadequate tools. In this study, we develop and characterize three inducible Cre mouse models for in vivo and temporally defined genetic manipulation in bipolar cell subtypes in the developing and adult mouse retina. These models serve as tools to elucidate the mechanisms that regulate the development and function of bipolar cell subtypes in the mouse retina.